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Cancer discovery. 2020 Apr 1. pii: 2159-8290.CD-19-1030. doi: 10.1158/2159-8290.CD-19-1030

Infant high grade gliomas comprise multiple subgroups characterized by novel targetable gene fusions and favorable outcomes.

Clarke M¹, Mackay A², Ismer B³, Pickles JC⁴, Tatevossian RG⁵, Newman S⁶, Bale TA⁷, Stoler I⁸, Izquierdo E⁹, Temelso S¹⁰, Carvalho DM¹¹, Molinari V¹², Burford A¹³, Howell L¹⁴, Virasami A¹⁵, Fairchild AR¹⁶, Avery A¹⁷, Chalker J¹⁸, Kristiansen M¹⁹, Haupfear K²⁰, Dalton JD²¹, Orisme W²², Wen J²³, Hubank M²⁴, Kurian KM²⁵, Rowe C²⁶, Maybury M²⁷, Crosier S²⁸, Knipstein J²⁹, Schuller U³⁰, Kordes U³¹, Kram DE³², Snuderl M³³, Bridges L³⁴, Martin AJ³⁵, Doey LJ³⁶, Al-Sarraj S³⁷, Chandler C³⁸, Zebian B³⁹, Cairns C⁴⁰, Natrajan R⁴¹, Boult JK⁴², Robinson SP⁴³, Sill M⁴⁴, Dunkel IJ⁴⁵, Gilheeney SW⁴⁶, Rosenblum MK⁴⁷, Hughes D⁴⁸, Proszek PZ⁴⁹, MacDonald TJ⁵⁰, Preusser M⁵¹, Haberler C⁵², Slavc I⁵³, Packer R⁵⁴, Ng HK⁵⁵, Caspi S⁵⁶, Popovic M⁵⁷, Faganel Kotnik B⁵⁸, Wood MD⁵⁹, Baird L⁶⁰, Davare MA⁶¹, Solomon DA⁶², Olsen TK⁶³, Brandal P⁶⁴, Farrell M⁶⁵, Cryan JB⁶⁶, Capra M⁶⁷, Karremann M⁶⁸, Schittenhelm J⁶⁹, Schuhmann MU⁷⁰, Ebinger M⁷¹, Dinjens WNM⁷², Kerl K⁷³, Hettmer S⁷⁴, Pietsch T⁷⁵, Andreiuolo F⁷⁶, Driever PH⁷⁷, Korshunov A⁷⁸, Hiddingh L⁷⁹, Worst BC⁸⁰, Sturm D⁸¹, Zuckermann M⁸², Witt O⁸³, Bloom T⁸⁴, Mitchell C⁸⁵, Miele E⁸⁶, Colafati GS⁸⁷, Diomedi-Camassei F⁸⁸, Bailey S⁸⁹, Moore AS⁹⁰, Hassall TE⁹¹, Lowis SP⁹², Tsoli M⁹³, Cowley MJ⁹⁴, Ziegler DS⁹⁵, Karajannis MA⁹⁶, Aquilina K⁹⁷, Hargrave DR⁹⁸, Carceller F⁹⁹, Marshall LV¹⁰⁰, von Deimling A¹⁰¹, Kramm CM¹⁰², Pfister SM¹⁰³, Sahm F¹⁰⁴, Baker SJ¹⁰⁵, Mastronuzzi A¹⁰⁶, Carai A¹⁰⁷, Vinci M¹⁰⁸, Capper D¹⁰⁹, Popov S¹¹⁰, Ellison DW¹¹¹, Jacques TS¹¹², Jones DTW¹¹³, Jones C¹¹⁴

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Abstract

Infant high grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histological review, methylation profiling, custom panel and genome/exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an 'intrinsic' spectrum of disease specific to the infant population. These included those with targetable MAP-kinase alterations, and a large proportion of remaining cases harboring gene fusions targeting ALK (n=31), NTRK1/2/3 (n=21), ROS1 (n=9) and MET (n=4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly supports the concept that infant gliomas require a change in diagnostic practice and management.

Publikations ID: 32238360
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